Chemical diversification of type II topoisomerase (Topo II) inhibitors remains indispensable to extend their anti-tumor therapeutic values which are limited by their side effects. Herein, we designed and synthesized a novel series of benzimidazole-chalcone hybrids (BCHs). These BCHs showed good inhibitory effect in the Topo II mediated DNA relaxation assay and anti-proliferative effect in 4 tumor cell lines. 4d and 4n were the most potent, with IC₅₀ values less than 5 μM, superior to etoposide. Mechanistic studies indicated that the BCHs functioned as non-intercalative Topo II catalytic inhibitors. Moreover, 4d and 4n demonstrated versatile properties against tumors, including inhibition on the colony formation and cell migration, and promotion of apoptosis of A549 cells. The structure-activity relationship and molecular docking analysis suggested possible contribution of the chalcone motif to the Topo II inhibitory and anti-proliferative potency. These results indicated that 4d and 4n could be promising lead compounds for further anti-tumor drug research.

Anti-tumor activity of Tremella fuciformis polysaccharides (TFPS) has been widely reported, but its mechanism remains poorly understood. In this study, we established an in vitro co-culture system (B16 melanoma cells and RAW 264.7 macrophage-like cells) to explore the potential anti-tumor mechanism of TFPS. Based on our results, TFPS exhibited no inhibition on the cell viability of B16 cells. However, significant apoptosis was observed when B16 cells were co-cultured with TFPS-treated RAW 264.7 cells. We further found that mRNA levels of M1 macrophage markers including iNOS and CD80 were significantly upregulated in TFPS-treated RAW 264.7 cells, while M2 macrophage markers such as Arg-1 and CD 206 remained unchanged. Besides, the migration, phagocytosis, production of inflammatory mediators (NO, IL-6 and TNF-α), and protein expression of iNOS and COX-2 were markedly enhanced in TFPS-treated RAW 264.7 cells. Network pharmacology analysis indicated that MAPK and NF-κB signaling pathways may be involved in M1 polarization of macrophages, and this hypothesis was verified by Western blot. In conclusion, our research demonstrated that TFPS induced apoptosis of melanoma cells by promoting M1 polarization of macrophages, and suggested TFPS may be applied as an immunomodulatory for cancer therapy.

Essential oils have attracted wide attention in recent years due to their extensive applications in natural functional ingredients, pharmaceutical preparations, biomedical products, and the cosmetics industry. In this study, the chemical compositions and biological activities of essential oils extracted from six Lamiaceae herbs, including Pogostemon cablin (Blanco) Benth. (PCEO), Perilla frutescens (L.) Britton (PFEO), Salvia japonica Thunb. (SJEO), Rosmarinus officinalis L. (ROEO), Lavandula angustifolia Mill. (LAEO), and Agastache rugosa (Fisch. & C. A. Mey.) Kuntze (AREO), were determined and analyzed. A total of 167 components were identified from the six essential oils by GC-MS analysis, with 35, 24, 47, 46, 54, and 37 components in PCEO, PFEO, SJEO, ROEO, LAEO, and AREO, respectively. Hierarchical cluster analysis of chemical compositions showed that the composition of the six essential oils was significantly different in content, and they were clearly divided into six classes. However, all of these six essential oils exhibited promising anti-inflammatory activity by inhibiting the expression of interleukin-1, interleukin-6, tumor necrosis factor-α, and cyclooxygenase-2 in rats with adjuvant arthritis, among which PFEO had the best performance. In addition, the six essential oils displayed significant cytotoxicity on B16 (IC₅₀ = 86.91–228.91 μg/mL) and LNCaP cell lines (IC₅₀ = 116.4–189.63 μg/mL). Meanwhile, all of them presented satisfactory antioxidant activity (IC₅₀ = 4.88–13.89 μg/mL) compared with Trolox C (IC₅₀ = 13.83 μg/mL), and SJEO (IC₅₀ = 7.93 μg/mL) served as an optimal candidate natural antioxidant by DPPH assay. Taken together, these results indicate that the six Lamiaceae essential oils manifest excellent and diverse biological activities, enabling them to be used as perfect natural functional ingredients in antioxidant, antitumor, or anti-arthritic drugs. This study provides more references for pharmaphylogeny research and drug discovery from folk medicinal plants.